The Control of Oocyte Differentiation in Flies. The proposal describes experiments designed to elucidate the manner by which in certain insects members of a clone of interconnected cells derived from oogonia are directed to enter different developmental pathways to generate an oocyte-nurse cell syncytium. Drosophila melanogaster serves a the model for all Diptera, and among this order are species that serve as vectors for numerous deadly tropical parasites. The experiments involve a combination of genetic immunological, cytochemical, and ultrastructural approaches. An organelle, the polyfusome, which connects all cells of the clone is thought to play a decisive role in the development and differentiation of the sibling cells. The study aims (1) to demonstrate how the polyfusome forms, (2) to clarify how it controls the orientation of mitotic spindles in space, (3) to investigate correlations between the ultrastructural architecture of the fusomal connections between sibling cells and the future differentiation of these cells, and (4) to determine some of the cytoskeletal proteins contained in polyfusomes. Next the morphology and cytochemical properties of normal polyfusomes will be contrasted with those of defective polyfusomes produced by females carrying sterility mutations that prevent oocyte differentiation. The continued differentiation of the oocyte requires subsequent interactions with specific somatic cells. To elucidate the nature of these interactions, specific mutations that block the formation and functioning of these cells will be studied, both morphologically and through the use of monoclonal antibodies directed against the surface antigens of these cells. Attempts will be made to generate temperature sensitive alleles of these mutations which allow normal development at permissive temperatures, but pathological development at the restrictive temperatures. Temperature shift experiments will then allow the time course of the interaction to be followed. Insights gained from these studies may suggest ways of sterilizing noxious species by interfering with these developmental reactions.